JP2016114574A - Supercritical fluid separator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a supercritical fluid separator which rapidly detects leakage when leakage of fluid occurs from a separation part.SOLUTION: The supercritical fluid separator comprises: a temperature sensor for detecting temperature of an exterior surface of a separation part; and a fluid leakage detector for detecting, on the basis of the output of the temperature sensor, leakage of fluid in the separation part when the temperature of the exterior surface of the separation part is a preset threshold value or lower after starting introduction of a moving phase into the separation part.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a supercritical fluid separation apparatus that separates sample components using a supercritical fluid.

  A chromatograph is used to measure the amount of pesticide residue in agricultural products and the amount of metabolites and drugs in blood, but it is necessary to extract the components to be measured as pretreatment. In order to extract a component to be measured, an extraction apparatus using a supercritical fluid that has a strong diffusivity into a sample and exhibits excellent solubility in many substances has been proposed (see Patent Document 1). .

  The extraction device of Patent Document 1 includes a plurality of extraction containers, and both or one of an inlet part for flowing a supercritical fluid and an outlet part for discharging a supercritical fluid in each extraction container is connected to the inlet part or the outlet part. It has a needle seal structure in which the flow path connection is made by inserting the tip of the needle provided at the end of the flow path to be extracted, and the extraction container for extracting the sample by automatically moving the needle It is configured to perform switching automatically.

  The holder holding the extraction container is thermally conductive, and the temperature of the holder is controlled to a predetermined temperature using an element such as a heater or a Peltier element. Liquid carbon dioxide and a modifier are supplied to the flow path connected to the inlet of the extraction container. A back pressure control valve is provided on the flow path connected to the outlet of the extraction container.

  The mobile phase composed of liquid carbon dioxide and a modifier is sent in a supercritical state in the flow path to the back pressure control valve by maintaining the back pressure at a constant high pressure state by the back pressure control valve. Thereby, the inside of the extraction container is filled with the supercritical fluid, and the components in the sample accommodated in the extraction container are extracted from the outlet portion of the extraction container. The extracted components are collected in a preparatory apparatus provided downstream thereof or analyzed by being introduced into a detector after being separated by an analytical column.

JP, 2014-160055, A

  The extraction container is provided with a cover that can be opened and closed so that the analyst can store the sample. If the cover is forgotten to be tightened or not fully tightened, the sample, extraction components, and mobile phase can be removed. Will leak out of the extraction container, but if the analyst is not aware of it, the extracted components, mobile phase, etc. will continue to scatter in the apparatus. The same problem also occurs when the piping connection between the extraction container and the flow path is insufficient. This is a problem that occurs even when the piping connection to the analytical column is insufficient in the supercritical fluid chromatograph.

  In view of the above, an object of the present invention is to make it possible to quickly detect a leakage of a fluid in a separation unit such as an extraction container or an analysis column.

  One embodiment of a supercritical fluid separation device according to the present invention is connected to a mobile phase liquid supply channel for supplying a mobile phase and a downstream side of the mobile phase liquid supply channel, and flows through the mobile phase liquid supply channel. A back pressure control valve that controls the pressure in the mobile phase liquid flow path so that the mobile phase is in a supercritical state, and is provided between the mobile phase liquid flow path and the back pressure control valve. After the introduction of the mobile phase to the separation unit based on the output of the separation unit that separates the sample components by the mobile phase from the flow path, the temperature sensor that detects the temperature of the outer surface of the separation unit, and the temperature sensor A fluid leakage detection unit that detects a fluid leakage in the separation unit when the temperature of the outer surface of the separation unit becomes equal to or lower than a preset threshold value.

  As a separation part in this supercritical fluid separation device, in addition to an analytical column that separates a sample for each component by passing a supercritical fluid, it has an internal space for accommodating the sample, and the internal space is defined as a supercritical fluid. The extraction container which extracts the component from a sample by filling with is mentioned.

  If the piping connection to the analytical column or extraction container is insufficient, or if the cap on the extraction container is forgotten to be tightened, liquid carbon dioxide as a solvent leaks from the piping connection part or the extraction container. It has been experimentally found that the outer surface temperature of the analytical column and the extraction container rapidly decreases due to the vaporization heat. Therefore, by monitoring the outer surface temperatures of these separation units with a temperature sensor, it is possible to detect a rapid decrease in the outer surface temperature of the separation unit, thereby detecting a fluid leak in the separation unit.

  In one embodiment of the supercritical fluid separation device according to the present invention, a temperature sensor that detects the temperature of the outer surface of the separation unit, and a separation after the introduction of the mobile phase to the separation unit is started based on the output of the temperature sensor Since it has a fluid leakage detector that detects fluid leakage in the separation part when the temperature of the outer surface of the part falls below a preset threshold value, it can quickly detect fluid leakage in the separation part Can do.

It is a schematic structure sectional view showing one example of a supercritical fluid separation device. It is sectional drawing which shows the needle seal structure in the exit part of the extraction container in the Example. It is a figure which shows an example of the time change of the temperature of the outer surface of an extraction container in the Example. It is a flowchart for demonstrating the detection operation of the fluid leak in the Example. It is a schematic block diagram which shows the other Example of a supercritical fluid separator.

  As the separation unit, there are an internal space for storing a sample, an inlet portion to which a mobile phase liquid flow channel is connected and a mobile phase liquid flow channel is introduced into the internal space, and a flow channel leading to a back pressure control valve. An extraction container having an outlet for connecting a sample extracted from the internal space together with the mobile phase to the back pressure control valve side may be mentioned. In the case of such an extraction container, not only when the pipe connection at the inlet and outlet is insufficient, but also when the forgotten tightening of the cap provided to accommodate the sample in the internal space or the tightening condition is insufficient, These problems can be quickly detected by detecting a decrease in the outer surface temperature of the extraction container with a temperature sensor.

  When the separation part is the extraction container, at least one of the inlet part or the outlet part of the extraction container is inserted with a movable needle provided at the end of the flow path to be connected to the inlet part or the outlet part. The needle seal structure that connects the flow path to the internal space by moving the needle provided at the end of the flow path to be connected to the inlet or outlet of the extraction container, Or you may further provide the needle movement mechanism which connects and disconnects to an exit part. If it does so, piping connection to the inlet part or outlet part of an extraction container will be made automatically and easily, and operations, such as washing and exchange of an extraction container, will become easy.

  Furthermore, the temperature sensor may be held by the needle moving mechanism so as to come into contact with the outer surface of the extraction container when the needle is inserted into the inlet or outlet of the extraction container. If it does so, it is not necessary to provide the temperature sensor which detects the outer surface temperature of an extraction container for every extraction container.

  As a more preferred embodiment, a plurality of extraction containers are provided, and the needle moving mechanism is configured to insert and connect a needle to an inlet portion or an outlet portion of the extraction container in which sample components are to be extracted. Thereby, it is possible to automatically and continuously extract components from a plurality of samples.

  An embodiment of the supercritical fluid separator will be described with reference to FIG.

  An extraction container 6 is housed in the container holder 2 as a separation unit that houses a sample from which a component is extracted. In this embodiment, four extraction containers 6 are provided, but the number of extraction containers 6 may be three or less or five or more. The extraction container 6 is made of a metal having a good thermal conductivity.

  The container holder 2 is provided with a hole for accommodating a lower part of the upper part of the extraction container 6 from the cap part 10. The container holder 2 is made of a metal having good thermal conductivity, and a heating block 4 is provided below the container holder 2. The heating block 4 is a thermally conductive metal member in which a temperature sensor such as a heater (not shown) and a thermistor (not shown) is embedded. The output of the heater embedded in the heating block 4 is controlled by the control unit 27 described later so that the temperature detected by the temperature sensor embedded in the heating block 4 becomes a set temperature (for example, 40 ° C.). Then, by controlling the output of the heater, the temperature of the entire container holder 2 is controlled to be constant at the set temperature.

  A cap part 10 is detachably mounted on the upper part of the extraction container 6. By removing the cap part 10, a sample can be accommodated in the extraction container 6, or the accommodated sample can be taken out. An outlet portion 11 is provided on the upper surface side of the cap portion 10. An inlet portion 8 is provided on the lower surface side of the extraction container 6.

  The inlet portion 8 and the outlet portion 11 have a needle seal structure in which flow path connection is performed by inserting a needle. The needle seal structure will be described later.

  Below the sample holder 2, there are provided an inlet needle 12 whose tip is directed vertically upward, and a needle moving mechanism 14 for moving the inlet needle 12 in the horizontal plane direction and the vertical direction. A mobile phase feeding flow path 15 is connected to the proximal end portion of the inlet side needle 12. A liquid feeding device 16 is connected to the mobile phase liquid feeding flow path 15. The liquid feeding device 16 includes a liquid feeding pump 16 a that feeds liquid carbon dioxide from the carbon dioxide container 18 and a liquid feeding pump 16 b that sends the modifier from the modifier container 20. A liquid solution 16 supplies a mixed solution of carbon dioxide and a modifier to the tip of the inlet needle 12.

  The inlet needle 12 is inserted into the inlet portion 8 of the extraction container 6 and connects the mobile phase liquid supply flow path 15 to the internal space of the extraction container 6. Although not shown, the heating block 4 of the sample holder 2 is provided with a hole leading to the inlet portion 8 of the extraction container 6 accommodated in the sample holder 2, and the inlet-side needle 12 extends from the hole to the inlet portion 8. Inserted into.

  Above the sample holder 2, there are provided an outlet side needle 24 whose tip is directed vertically downward, and a needle moving mechanism 22 for moving the outlet side needle 24 in the horizontal plane direction and the vertical direction. An extraction channel 23 is connected to the proximal end portion of the outlet side needle 24. The extraction flow path 23 communicates with the sorting device 32, and a back pressure control valve (BPR) 30 is provided on the extraction flow path 23.

  The outlet side needle 24 is inserted into the outlet portion 11 of the extraction container 6 and connects the extraction flow path 23 to the internal space of the extraction container 6. A sensor holder 26 is provided at the outlet needle 24, and a temperature sensor 36 (see FIG. 2) is provided at the lower end of the sensor holder 26. The temperature sensor 36 contacts the outer surface of the extraction container 6 when the outlet-side needle 24 is inserted into the outlet portion 11 of the extraction container 6, and detects the temperature of the outer surface of the extraction container 6.

  In the supercritical fluid separation device of this embodiment, an inlet side needle 12 and an outlet side needle 24 are inserted into an inlet portion 8 and an outlet portion 11 of an extraction container 6 in which a sample for extracting a component is accommodated, respectively. The apparatus 16 is driven to supply a mobile phase composed of liquid carbon dioxide and a modifier to the extraction vessel 6. At this time, the back pressure control valve 30 causes the pressure in the system constituted by the mobile phase liquid supply flow path 15, the extraction container 6 and the extraction flow path 23 upstream of the back pressure control valve 30 to exceed the mobile phase. The pressure is controlled to a critical state.

  When the extraction container 6 is filled with the supercritical fluid, components are extracted from the sample accommodated in the extraction container 6, and the components are introduced into the sorting device 32 through the extraction flow path 23 together with the mobile phase and collected. .

  Here, the needle seal structure at the outlet 11 of the extraction container 6 and the structure of the sensor holder 26 will be described with reference to FIG. The inlet portion 8 of the extraction container 6 also has a needle seal structure, but the structure is the same as the needle seal structure of the outlet portion 11.

  The outlet portion 11 of the extraction container 6 is provided in a cap portion 10 attached to the upper portion of the extraction container 6. A screw in the circumferential direction is provided at the upper part of the inner surface of the main body portion of the extraction container 6, and a screw is also provided at the lower part of the outer peripheral surface of the cap part 10, so that the cap part 10 is rotated relative to the main body part of the extraction container 6. Thus, the cap portion 10 can be tightened and fixed to the main body portion, or the cap portion 10 can be loosened and removed from the main body portion.

  The outlet 11 is provided with a hole 11 a for inserting the tip of the outlet side needle 24 and a hole 11 b for connecting the hole 11 a to the internal space of the extraction container 6. The inner diameter of the hole 11 a is larger than the outer diameter of the outlet side needle 24, and the inner diameter of the hole 11 b is smaller than the outer diameter of the outlet side needle 24. The joint portion 11c between the hole 11a and the hole 11b has a tapered shape with a smaller inner diameter as it goes downward, and the tip of the outlet needle 24 is pressed against the joint portion 11c, so that the outlet needle 24 The inner flow path and the hole 11b are connected while maintaining a sealing property.

  A sensor holder 26 is attached to the distal end side of the outlet side needle 24. The sensor holder 26 is a cylindrical member that surrounds the outer peripheral surface of the outlet side needle 24, and a temperature sensor 36 such as a thermistor is provided on the lower end surface thereof. An elastic member 38 such as a coil spring that extends and contracts in the axial direction of the outlet side needle 24 is accommodated inside the sensor holder 26. The elastic member 38 has an upper end engaged with a hook-shaped protrusion 34 provided on the outlet needle 24, and a lower end engaged with the sensor holder 26. The sensor holder 26 is biased toward the distal end side of the outlet side needle 24 by an elastic member 38.

  The temperature sensor 36 provided on the lower end surface of the sensor holder 26 is in contact with the edge of the hole 11a of the outlet part 11 when the outlet side needle 24 is inserted into the hole 11a of the outlet part 11, and the elastic force of the elastic member 38. Is pressed against the edge of the hole 11a and comes into close contact with the edge. The temperature sensor 35 detects the outer surface temperature of the cap unit 10.

  Returning to FIG. 1 and continuing the description, the control for controlling the output of the heater embedded in the heating block 4, the operation of the needle moving mechanisms 14 and 22, the operation of the liquid feeding device 16, and the operation of the back pressure control valve 30. A portion 27 is provided. The control unit 27 is realized by a dedicated computer or a general-purpose personal computer. The control unit 27 includes a fluid leak detection unit 28 having a function of detecting a fluid leak from the extraction container 6 and a threshold holding unit 29 that holds a threshold used by the fluid leak detection unit 28 for detecting the fluid leak. It has. The threshold value holding unit 29 holds a threshold value (for example, a set value of −30%) determined based on the set value for temperature adjustment of the extraction container 6.

  Based on the output signal from the temperature sensor 36, the fluid leak detection unit 28 holds the outer surface temperature of the extraction container 6 (the temperature of the outlet unit 11) after the start of component extraction in the threshold holding unit 29. When it becomes below a threshold value, it is comprised so that the fluid leakage from the extraction container 6 may be detected.

  FIG. 3 is an example of a change over time in the temperature detected by the temperature sensor 36 when the cap unit 10 is forgotten to be tightened.

  In order to improve the extraction efficiency of the components, the extraction container 6 is heated to a set temperature by a heater embedded in the heating block 4, and after the temperature of the extraction container 6 is stabilized, the liquid feeding device 16 is driven to extract the extraction container 6. The supercritical fluid is supplied to and the extraction of the components is started. However, when the cap part 10 of the extraction container 6 is forgotten to be tightened or when the tightening condition is insufficient, the mobile phase leaks from the tightening part of the cap part 10 and vaporizes, and the extraction container is caused by the heat of vaporization. The temperature of the outer surface of 6, particularly the cap portion 10, decreases rapidly.

In the example of FIG. 3, after the liquid feeding device 16 starts feeding the mobile phase at time T ₀ when the temperature of the extraction container 6 is stabilized, the temperature detected by the temperature sensor 36 suddenly decreases, and at time T ₁ The detected temperature is below the threshold. In the experiment, when the set temperature of the temperature control of the extraction container 6 is 40 ° C. and the threshold value is 28 ° C., the extraction container 45 seconds after the temperature of the extraction container 6 is stabilized and the component extraction operation is started. A fluid leak from 6 was detected.

  The operation for detecting fluid leakage from the extraction container 6 will be described with reference to FIG. 1 and FIG.

  First, the temperature of the extraction container 6 is stabilized at a set temperature by a heater (not shown) embedded in the heating block 4. Before or after the temperature control is started, the inlet side needle 12 and the outlet side needle 24 are inserted into the inlet portion 8 and the outlet portion 11 of the extraction container 6 for extracting the components, respectively. After the temperature of the extraction container 6 is stabilized, the mobile phase is supplied to the extraction container 6 by the liquid feeding device 16.

  The temperature of the cap unit 10 of the extraction container 6 detected by the temperature sensor 36 is taken into the control unit 27 at regular intervals, and the detected temperature and the threshold value are sequentially compared. When the temperature detected by the temperature sensor 36 exceeds the threshold value, the supply of the mobile phase by the liquid delivery device 16 is continued until the extraction of the components is completed. When the temperature detected by the temperature sensor 36 is equal to or lower than the threshold value, fluid leakage from the extraction container 6 is detected, and that fact is displayed on the display unit such as a liquid crystal display connected to the control unit 27 or the lamp is turned on. In such a case, a warning is given to the analyst, the operation of the liquid feeding device 16 is stopped, and the component extraction operation is terminated.

  Next, another embodiment of the supercritical fluid separator will be described with reference to FIG.

  The supercritical fluid separation device of this embodiment is constituted by a liquid feeding device 46 having a liquid feeding pump 46 a for feeding liquid carbon dioxide from the carbon dioxide container 42 and a liquid feeding pump 46 b for feeding a modifier from the modifier container 44. The mixed solution of carbon dioxide and modifier is sent as a mobile phase through the analysis flow path 40 (mobile phase liquid flow path). On the analysis flow path 40, a sample injection section 48, an analysis column 50, a detector 54, and a back pressure control valve (BPR) 56 are provided from the upstream side.

  The back pressure control valve 56 controls the pressure in the analysis flow path 40 so that the mobile phase flowing through the analysis flow path 40 is in a supercritical state. The sample injection unit 48 is a sample injection device such as an autosampler that injects a sample into the analysis flow path 40. The analysis column 50 is an analysis column for supercritical fluid chromatography, and the sample injected into the analysis flow path 40 by the sample injection unit 48 is separated for each component. The sample components separated by the analysis column 50 are guided to the detector 54 and detected. Although not shown, the analytical column 50 is accommodated in a column oven whose internal temperature is controlled at a constant temperature.

  Operations of the liquid feeding device 46 and the back pressure control valve 56 are controlled by the control unit 58. The control unit 58 includes a fluid leak detection unit 60 for detecting a fluid leak from a pipe connection portion of the analysis column 50 and a threshold holding unit 62 for holding a threshold used for detecting the fluid leak. Yes. A temperature sensor 52 for detecting the outer surface temperature of the analysis column 50 is provided, and an output signal of the temperature sensor 52 is taken into the control unit 58. The threshold value holding unit 62 holds a value (for example, a set temperature of −30%) determined based on the set temperature of the column oven in which the analysis column 50 is accommodated.

  If the piping connection to the analytical column 50 is insufficient, the mobile phase containing the liquid carbon dioxide leaks at the pipe connection portion when the mobile phase liquid feeding is started by the liquid feeding device 46. The outer surface temperature of the analytical column 50 is lowered by the heat of vaporization of the phase.

  Based on the output signal from the temperature sensor 52, the fluid leak detection unit 60 holds the temperature of the outer surface of the analytical column 50 after the mobile phase liquid feeding by the liquid feeding device 46 is held in the threshold holding unit 62. When the value falls below the threshold value, fluid leakage in the analysis column 50 is detected. It is preferable that the control unit 58 is configured to stop the operation of the liquid feeding device 46 and issue a warning to the analyst when a fluid leak is detected.

DESCRIPTION OF SYMBOLS 2 Container holder 4 Heating block 6 Extraction container 8 Inlet part 10 Cap part 11 Outlet part 12 Inlet side needle 14, 22 Needle moving mechanism 15 Mobile phase liquid supply flow path 16, 46 Liquid supply apparatus 16a, 16b, 46a, 46b Liquid supply Pump 18, 42 Carbon dioxide container 20, 44 Modifier container 23 Extraction flow path 24 Outlet side needle 26 Sensor holder 27, 58 Control unit 28, 60 Fluid leak detection unit 29, 62 Threshold holding unit 30, 56 Back pressure control Valve 32 Sorting device 34 Protrusion 36, 52 Temperature sensor 38 Elastic member 40 Analysis flow path 50 Analysis column 54 Detector

Claims (5)

A mobile phase feeding flow path for feeding a mobile phase;
A back pressure control valve that is connected to the downstream side of the mobile phase liquid flow path and controls the pressure in the mobile phase liquid flow path so that the mobile phase flowing through the mobile phase liquid flow path is in a supercritical state. When,
A separation unit that is provided between the mobile phase liquid flow path and the back pressure control valve and separates sample components by the mobile phase from the mobile phase liquid flow path;
A temperature sensor for detecting the temperature of the outer surface of the separation unit;
Based on the output of the temperature sensor, when the temperature of the outer surface of the separation unit after the introduction of the mobile phase into the separation unit becomes equal to or lower than a preset threshold value, the fluid in the separation unit A supercritical fluid separation device comprising: a fluid leakage detection unit that detects leakage.   The separation unit includes an internal space for storing a sample, an inlet portion to which the mobile phase liquid flow path is connected and a mobile phase from the mobile phase liquid flow path is introduced into the internal space, and the back pressure control valve. The supercritical fluid separation device according to claim 1, wherein the supercritical fluid separation device is an extraction container having an outlet connected to a flow path leading to the sample and extracted from the internal space together with the mobile phase to the back pressure control valve side. At least one of the inlet portion or the outlet portion of the extraction container is inserted into a movable needle provided at an end portion of the flow channel to be connected to the inlet portion or the outlet portion. It has a needle seal structure that connects to the internal space,
A needle that connects and disconnects the needle from the inlet or outlet by moving the needle provided at the end of the flow path to be connected to the inlet or outlet of the extraction container The supercritical fluid separation device according to claim 2, further comprising a moving mechanism.   The ultra-high temperature sensor according to claim 3, wherein the temperature sensor is held by the needle moving mechanism so as to contact an outer surface of the extraction container when the needle is inserted into the inlet portion or the outlet portion of the extraction container. Critical fluid separator. A plurality of the extraction containers;
The supercritical fluid separation device according to claim 3 or 4, wherein the needle moving mechanism is connected by inserting the needle into the inlet portion or the outlet portion of an extraction container in which sample components are to be extracted.

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